2-(purin-9-yl)-tetrahydrofuran-3,4-diol derivatives

Abstract

There are provided according to the invention, novel compounds of formula (I) wherein R<1>, R<2 >and R<3 >are as described in the specification, processes for preparing them, formulations containing them and their use in therapy for the treatment of inflammatory disease.

What is claimed is:  
     
       1. A compound of formula (I):                    
       wherein R 1  and R 2  independently represent a group selected from:  
       (i) C 3-8 cycloalkyl-;  
       (ii) hydrogen;  
       (iii) aryl 2 CHCH 2 —;  
       (iv) C 3-8 cycloalkylC 1-6 alkyl-;  
       (v) C 1-8 alkyl-;  
       (vi) arylC 1-6 alkyl-;  
       (vii) R 4 R 5 N—C 1-6 alkyl-;  
       (viii) C 1-6 alkyl-CH(CH 2 OH)—;  
       (ix) arylC 1-5 alkyl-CH(CH 2 OH)—;  
       (x) arylC 1-5 alkyl-C(CH 2 OH) 2 —;  
       (xi) C 3-8 cycloalkyl independently substituted by one or more —(CH 2 ) p R 6  groups;  
       (xii) H 2 NC(═NH)NHC 1-6 alkyl-;  
       (xiii) a group of formula                    
        or such a group in which one methylene carbon atom adjacent to X, or both if such exist, is substituted by methyl;  
       (xiv) —C 1-6 alkyl-OH;  
       (xv) —C 1-8 haloalkyl;  
       (xvi) a group of formula                    
       (xvii) aryl; and  
       (xviii) —(CH 2 ) f SO 2 NH g (C 1-4 alkyl-) 2-g  or —(CH 2 ) f SO 2 NH g (arylC 1-4 alkyl-) 2-g ;  
       R 3  represents methyl, ethyl, —CH═CH 2 , n-propyl, —CH 2 CH═CH 2 , —CH═CHCH 3 , isopropyl, isopropenyl, cyclopropyl, cyclopropenyl, cyclopropylmethyl, cyclopropenylmethyl, —CH(OH)CH 3 , —(CH 2 ) q halogen, —(CH 2 ) h Y(CH 2 ) i H, —(CH 2 ) k Z, —(CH 2 ) h CO(CH 2 ) o H, —(CH 2 ) r S(O) t (CH 2 ),H or —(CH 2 ) k C((CH 2 ) u H)═NO(CH 2 )H;  
       Y represents O, S or N(CH 2 ) j H;  
       Z represents —COO(CH 2 ) i H or —CON(CH 2 ) m H((CH 2 ) n H);  
       a and b independently represent an integer 0 to 4 provided that a+b is in the range 3 to 5;  
       c, d and e independently represent an integer 0 to 3 provided that c+d+e is in the range 2 to 3;  
       f represents 2 or 3 and g represents an integer 0 to 2;  
       p represents 0 or 1;  
       q represents an integer 0 to 3;  
       h represents an integer 0 to 2;  
       i represents an integer 0 to 2 such that h+i is in the range 0 to 3;  
       j represents an integer 0 to 2 such that h+i+j is in the range 0 to 3;  
       k represents 0 or 1;  
       l represents 1 or 2, such that k+l is in the range 1 to 2;  
       m and n independently represent an integer 0 to 2 such that k+m+n is in the range 0 to 2;  
       o represents an integer 0 to 2 such that h+o is in the range 0 to 2;  
       r and s independently represent 1 or 2 such that r+s is in the range 2 to 3;  
       t represents 1 or 2;  
       u and v independently represent 0 or 1 such that k+u+v is in the range 0 to 1;  
       R 4  and R 5  independently represent hydrogen, C 1-6 alkyl, aryl, arylC 1-6 alkyl- or NR 4 R 5  together may represent pyridinyl, pyrrolidinyl, piperidinyl, morpholinyl, azetidinyl, azepinyl, piperazinyl, N—C 1-6 alkylpiperazinyl or 2-(1-methyl-1H-imidazol-4-yl)-;  
       R 6  represents —OH, —NH 2 , —NHCOCH 3  or halogen;  
       R 7  represents hydrogen, —C 1-6 alkyl, —C 1-6 alkylaryl or —COC 1-6 alkyl;  
       X represents NR 7 , O, S, SO or SO 2 ;  
       and salts and solvates thereof. 
     
     
       2. A compound of formula (I) according to  claim 1  wherein R 3  represents methyl, ethyl or n-propyl and R 7  represents hydrogen, —C 1-6 alkyl, —C 1-6 alkylaryl or —COCH 3 . 
     
     
       3. A compound of formula (I) according to  claim 1  wherein R 1  and R 2  do not both represent hydrogen. 
     
     
       4. A compound of formula (I) according to  claim 1  wherein R 1  represents C 3-8 cycloalkyl, aryl 2 CHCH 2 —, arylC 1-6 alkyl-, C 1-8 alkyl-, aryl, —(CH 2 ) f SO 2 NH g (C 1-4 alkyl) 2-g , tetrahydropyran-n-yl or tetrahydrothiopyran-n-yl where n is 3 or 4, C 3-8 cycloalkylC 1-6 alkyl-, hydrogen, or R 4 R 5 N—C 1-6 alkyl- where NR 4 R 5  together represents piperidinyl or morpholinyl. 
     
     
       5. A compound of formula (I) according to  claim 1  wherein R 1  represents C 1-6 alkyl-CH(CH 2 OH)—, 1,1-dioxo-hexahydro-1-λ-6-thiopyran-4-yl, N-acetyl-piperidin-4-yl, 1S-hydroxymethyl-2-phenylethyl, piperidin-4-yl, or 1-oxo-hexahydro-1-λ-4-thiopyran-4-yl. 
     
     
       6. A compound of formula (I) according to  claim 1  wherein R 1  represents —CH 2 CHPh 2 , —CH(Et) 2  or phenylethyl. 
     
     
       7. A compound of formula (I) according to  claim 1  wherein R 2  represents —C 1-6 alkyl-OH, H 2 NC(═NH)NHC 1-6 alkyl-, R 4 R 5 NC 1-6 alkyl- where NR 4 R 5  together represents pyridinyl, piperidinyl, morpholinyl or 2-(1-methyl-1H-imidazol-4-yl), arylC 1-5 alkylCH(CH 2 OH)—, aryl, C 3-8 cycloalkylC 1-6 alkyl-, tetrahydro-1,1-dioxide thiophen-3-yl, C 3-8 cycloallkyl, C 1-6 alkyl-CH(CH 2 OH)—, arylC 1-6 alkyl-, pyrrolidin-3-yl, 2-oxopyrrolidin-4-yl, 2-oxopyrrolidin-5yl, piperidin-3-yl, aryl C 1-6 alkyl, C 3-8 cycloalkyl independently substituted by one or more —(CH 2 ) p R 6  groups, or piperidin-4-yl in which the ring nitrogen is optionally substituted by C 1-6 alkyl. 
     
     
       8. A compound of formula (I) according to  claim 1  wherein R 2  represents C 1-8 alkyl or R 4 R 5 NC 1-6 alkyl- wherein R 4  and R 5  independently represent hydrogen or aryl or R 4 R 5 N together represents pyrrolidinyl. 
     
     
       9. A compound of formula (I) according to  claim 1  wherein R 2  represents piperidin-1-ylethyl or 2-(1-methyl-1H-imidazol-4-yl)ethyl. 
     
     
       10. A compound of formula (I) according to  claim 1  wherein R 3  represents —CH═NOH, cyclopropyl, —COOCH 3 , —COOCH 2 CH 3 , —CH 2 OH, —CH(OH)CH 3  or halogen. 
     
     
       11. A compound of formula (I) according to  claim 1  wherein R 3  represents methyl, ethyl or n-propyl. 
     
     
       12. A compound of formula (I) according to  claim 1  wherein R 3  represents ethyl or —CH 2 OH. 
     
     
       13. A compound of formula (I) according to  claim 12  wherein R 3  represents ethyl. 
     
     
       14. A compound of formula (I) according to  claim 1  wherein R 4  and R 5  independently represent hydrogen, C 1-6 alkyl, aryl, arylC 1-6 alkyl- or NR 4 R 5  together may represent pyrrolidinyl, piperidinyl, morpholinyl, azetidinyl, azepinyl, piperazinyl or N—C 1-6 alkylpiperazinyl. 
     
     
       15. A compound of formula (I) according to  claim 14  wherein R 4  and R 5  independently represent hydrogen, C 1-6 alkyl or aryl or NR 4 R 5  together represent pyrrolidinyl, piperidinyl, morpholinyl, azetidinyl, azepinyl or N-methylpiperazinyl. 
     
     
       16. A compound of formula (I) according to  claim 1  which is (2R,3R,4S,5S)-2-[6-(2,2-Diphenyl-ethylamino)-2-(2-piperidin-1-yl-ethylamino)-purin-9-yl]-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol or a salt or solvate thereof. 
     
     
       17. A compound of formula (1) according to  claim 1  which is (2R,3R,4S,5S)-2-(3-Ethyl-isoxazol-5-yl)-5-[6-phenethylamino-2-(2-piperidin-1-yl-ethylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol or a salt or solvate thereof. 
     
     
       18. A compound of formula (1) according to  claim 1  which is (2S,3S,4R,5R)-2(3-Ethyl-isoxazol-5-yl)-5-[6-(1-ethyl-propylamino)-2-(2-piperidin-1-yl-ethylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol or a salt or solvate thereof. 
     
     
       19. A compound of formula (1) according to  claim 1  which is (2R,3R,4S,5S)-2-{6-(1-Ethyl-propylamino)-2-[2-(1-methyl-1H-imidazol-4-yl)-ethylamino]-purin-9-yl}-5-(3-hydroxymethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol or a salt or solvate thereof. 
     
     
       20. A compound of formula (I) according to  claim 1  which is (2R,3R,4S,5S)-2-[6-(2,2-Diphenyl-ethylamino)-2-(2-morpholin-4-yl-ethylamino)-purin-9-yl]-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-[6-(2,2-Diphenyl-ethylamino)-2-(2-hydroxy-ethylamino)-purin-9-yl]-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5{-6-(1-ethyl-propylamino)-2-[2-(1-methyl-1H-imidazol-4-yl)-ethylamino]-purin-9-yl}-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-{6-(3,3-Dimethyl-butylamino)-2-[2-(1-methyl-1H-imidazol-4-yl)-ethylamino]-purin-9-yl}-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-[6-(cyclopentylamino)-2-(2-piperidin-1-yl-ethylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol; N-{2-[9-[5S-(3-Ethyl-isoxazol-5-yl)-3R,4S-dihydroxy-tetrahydro-furan-2R-yl]-6-(tetrahydro-thiopyran-4-ylamino)-9H-purin-2-ylamino]-ethyl}-guanidine; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-[6(3-fluoro-4-hydroxy-phenylamino)-2-(2-piperidin-1-yl-ethylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol; 2-[9-[5S-(3-Ethyl-isoxazol-5-yl)-3R,4S-dihydroxy-tetrahydro-furan-2R-yl]-2-(2-piperidin-1-yl-ethylamino)-9H-purin-6-ylamino]-ethanesulfonic acid methylamide; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-[2-(2-piperidin-1-yl-ethylamino)-6-(tetrahydro-thiopyran-4-ylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-[2-(2-pyridin-2-yl-ethylamino)-6-(tetrahydro-pyran-4-ylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-[2-(2-piperidin-1-yl-ethylamino)-6-(tetrahydro-pyran-4-ylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-[2(1S-hydroxymethyl-2-phenyl-ethylamino)-6-(tetrahydro-pyran-4-ylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-{6-(2,2-Diphenyl-ethylamino)-2-[2-(pyridin-2-ylamino)-ethylamino]-purin-9-yl}-3-(5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; (2R,3R,4S,5 S)-2-[6-(2,2-Diphenyl-ethylamino)-2-(1S-hydroxymethyl-2-phenyl-ethylamino)-purin-9-yl]-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; 4-(2-{6-Amino-9-[5S-(3-ethyl-isoxazol-5-yl)-3R,4S-dihydroxy-tetrahydrofuran-2R-yl]-9H-purin-2-ylamino}-ethyl)-benzenesulfonamide; (2R,3R,4S,5S)-2-[2-(trans-4-Amino-cyclohexylamino)-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-{6-(3-iodo-benzylamino)-2-[2-(1-methyl-1H-imidazol-4-yl)-ethylamino]-purin-9-yl}-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-{6-(2-Cyclohexyl-ethylamino)-2-[2-(1-methyl-1H-imidazol-4-yl)-ethylamino]-purin-9-yl}-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-[6-(2-Cyclohexyl-ethylamino)-2-(1S-hydroxymethyl-2-phenyl-ethylamino)-purin-9-yl]-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; N-(2-{6-(2,2-Diphenyl-ethylamino)-9-[5S-(3-ethyl-isoxazol-5-yl)-3R,4S-dihydroxy-tetrahydro-furan-2R-yl]-9H-purin-2-ylamino}-ethyl)-guanidine; N-(4-{6-(2,2-Diphenyl-ethylamino)-9-[5S-(3-ethyl-isoxazol-5-yl)-3R,4S-dihydroxy-tetrahydro-furan-2R-yl]-9H-purin-2-ylamino}-cyclohexyl)-acetamide; 2-[9-[5S-(3-Ethyl-isoxazol-5-yl)-3R,4S-dihydroxy-tetrahydro-furan-2R-yl]-2-(2- guanidino-ethylamino)-9H-purin-6-ylamino]-ethanesulfonic acid methylamide; N-(2-{6-(1,1-Dioxo-hexahydro-1.lambda.6-thiopyran-4-ylamino)-9-[5S-(3-ethyl-isoxazol-5-yl)-3R,4S-dihydroxy-tetrahydro-furan-2R-yl]-9H-purin-2-ylamino}-ethyl)-guanidine; 2-[9-[5S-(3-Ethyl-isoxazol-5-yl)-3R,4S-dihydroxy-tetrahydro-furan-2R-yl]-2-(1S-hydroxymethyl-2-phenyl-ethylamino)-9H-purin-6-ylamino]-ethanesulfonic acid methylamide; 1-{4-[9-[5S-(3-Ethyl-isoxazol-5-yl)-3R,4S-dihydroxy-tetrahydro-furan-2R-yl]-2-(1S-hydroxymethyl-2-phenyl-ethylamino)-9H-purin-6-ylamino]-piperidin-1-yl}-ethanone; 1-(4-{2-(trans-4-Amino-cyclohexylamino)-9-[5S-(3-ethyl-isoxazol-5-yl)-3R,4S-dihydroxy-tetrahydro-furan-2R-yl]-9H-purin-6-ylamino}-piperidin-1-yl)-ethanone; (2R,3R,4S,5S)-2-(3-Ethyl-isoxazol-5-yl)-5-[2-(2-pyridin-2-yl-ethylamino)-6-(tetrahydro-thiopyran-4-ylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-[6-(1,1-Dioxo-hexahydro-1.lambda.6-thiopyran-4-ylamino)-2-(2-piperidin-1-yl-ethylamino)-purin-9-yl]-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-[2-(trans-4-Amino-cyclohexylamino)-6-(1,1-dioxo-hexahydro-1.lambda.6-thiopyran-4-ylamino)-purin-9-yl]-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; N-(2-{6-(1-Acetyl-piperidin-4-ylamino)-9-[5S-(3-ethyl-isoxazol-5-yl)-3R,4S-dihydroxy-tetrahydro-furan-2R-yl]-9H-purin-2-ylamino}-ethyl)-guanidine; N-{2-[9-[5S-(3-ethyl-isoxazol-5-yl)-3R,4S-dihydroxy-tetrahydro-furan-2R-yl]-6-(piperidin-4-ylamino)-9H-purin-2-ylamino]-ethyl}-guanidine; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-[2-(1S-hydroxymethyl-2-phenyl-ethylamino)-6-(tetrahydro-thiopyran-4-ylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol; (2S,3S,4R,5R)-2-(3-ethyl-isoxazol-5-yl)-5-[2-(1S-hydroxymethyl-2-phenyl-ethylamino)-6-(1-oxo-hexahydro-1.lambda.4-thiopyran-4-ylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol); (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-[6-(1-ethyl-propylamino)-2-(1S-hydroxymethyl-2-phenyl-ethylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-[6-(1-ethyl-propylamino)-2-(pyrrolidin-3R-ylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-[6-(1-ethyl-propylamino)-2-(2-pyridin-2-yl-ethylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol; (2S,3 S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-[6-(1-ethyl-propylamino)-2-(2-morpholin-4-yl-ethylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-[2-(trans-4-Amino-cyclohexylamino)-6-(1-ethyl-propylamino)-purin-9-yl]-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; N-{2-[9-[5S-(3-Ethyl-isoxazol-5-yl)-3R,4S-dihydroxy-tetrahydro-furan-2R-yl]-6-(1-ethyl-propylamino)-9H-purin-2-ylamino]-ethyl}-guanidine; (2R,3R,4S,5S)-2-[6-(3,3-Dimethyl-butylamino)-2-(2-piperidin-1-yl-ethylamino)-purin-9-yl]-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-[6-(3,3-Dimethyl-butylamino)-2-(2-morpholin-4-yl-ethylamino)-purin-9-yl]-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol]; (2R,3R,4S,5S)-2-{6-Benzylamino-2-[2-(1-methyl-1H-imidazol-4-yl)-ethylamino]-purin-9-yl}-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-[6-Benzylamino-2-(2-piperidin-1-yl-ethylamino)-purin-yl]-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-[6-(1S-hydroxymethyl-2-phenyl-ethylamino)-2-(2-piperidin-1-yl-ethylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-[2-(Cyclopentylamino)-6-(1-ethyl-propylamino)-purin-9-yl]-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-[2-(3,4-Dimethoxyphenyl-ethylamino)-6-(1-ethyl-propylamino)-purin-9-yl]-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-[2-(4-tetrahydropyranyl-amino)-6-(1-ethyl-propylamino)-purin-9-yl]-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-[2-(1-Benzyl-pyrrolidin-3S-1-ylamino)-6-(1-ethyl-propylamino)-purin-9-yl]-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; 5-(5R-{6-(1-Ethyl-propylamino)-2-[2-(1-methyl-1H-imidazol-4-yl)-ethylamino]-purin-9-yl}-3 S,4R-dihydroxy-tetrahydro-furan-2S-yl)-isoxazole-3-carbaldehyde oxime; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-[6-(1S-hydroxymethyl-2-phenyl-ethylamino)-2-(2-morpholin-4-yl-ethylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-[6-benzylamino-2-(2-pyridin-2-yl-ethylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-{6-(1-ethyl-propylamino)-2-[2-(pyridin-2-ylamino)-ethylamino]-purin-9-yl}-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-[6-(1-Ethyl-propylamino)-2-(2-piperidin-1-yl-ethylamino)-purin-9-yl]-5-[3-(1-hydroxy-ethyl)-isoxazol-5-yl]-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-[6-(1-Ethyl-propylamino)-2-(2-piperidin-1-yl-ethylamino)-purin-9-yl]-5-(3-methyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-[6-(1-Ethyl-propylamino)-2-(2-piperidin-1-yl-ethylamino)-purin-9-yl]-5-(3-propyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-[6-(1-Ethyl-propylamino)-2-(2-piperidin-1-yl-ethylamino)-purin-9-yl]-5-(3-hydroxymethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-{6-(1-Ethyl-propylamino)-2-[2-(1-methyl-1H-imidazol-4-yl)-ethylamino]-purin-9-yl}-5-[3(1-hydroxy-ethyl)-isoxazol-5-yl]-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-{6-(1-Ethyl-propylamino)-2-[2-(1-methyl-1H-imidazol-4-yl)-ethylamino]-purin-9-yl}-5-(3-methyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-{6-(1-Ethyl-propylamino)-2-[2-(1-methyl-1H-imidazol-4-yl)-ethylamino]-purin-9-yl}-5-(3-propyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-{6-(1S-hydroxymethyl-2-phenyl-ethylamino)-2-[2-(pyridin-2-ylamino)-ethylamino]-purin-9-yl}-tetrahydro-furan-3,4-diol; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-[6-(1S-hydroxymethyl-2-phenyl-ethylamino)-2-(2-pyrrolidin-1-yl-ethylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-[2-(2-Amino-ethylamino)-6-(1S-hydroxymethyl-2-phenyl-ethylamino)-purin-9-yl]-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-[6-(3-iodo-benzylamino)-2-(2-piperidin-1-yl-ethylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol; (2R,3R,4S,5S)-2-[2-Ethylamino-6-(3-iodo-benzylamino)-purin-9-yl]-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3,4-diol; (2S,3S,4R,5R)-2-(3-Bromo-isoxazol-5-yl)-5-[6-(1-ethyl-propylamino)-2-(2-piperidin-1-yl-ethylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol; 5-(5R-{6-(1-Ethyl-propylamino)-2-[2-(1-methyl-1H-imidazol-4-yl)-ethylamino]-purin-9-yl}-3S,4R-dihydroxy-tetrahydro-furan-2S-yl)-isoxazole-3-carboxylic acid ethyl ester; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-[6-(1S-hydroxymethyl-2-methyl-propylamino)-2-(2-pyrrolidin-1-yl-ethylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-[6-(1S-hydroxymethyl-2-methyl-propylamino)-2-(2-piperidin-1-yl-ethylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-{6-(1S-hydroxymethyl-2-methyl-propylamino)-2-[2-(pyridin-2-ylamino)ethylamino]-purin-9-yl}-tetrahydro-furan-3,4-diol; (2S,3S,4R,5R)-2-(3-Ethyl-isoxazol-5-yl)-5-{6-(1S-hydroxymethyl-2-methyl-propylamino)-2-(1S-hydroxymethyl-2-phenyl-ethylamino)-purin-9-yl}-tetrahydro-furan-3,4-diol; or a salt or solvate of any one thereof. 
     
     
       21. A pharmaceutical composition comprising a compound of formula (I) as defined in  claim 1  or a pharmaceutically acceptable salt or solvate thereof in admixture with one or more physiologically acceptable diluents or carriers. 
     
     
       22. A pharmaceutically acceptable salt of a compound of formula (I) as defined in  claim 1 . 
     
     
       23. A process for preparation of a compound of formula (I) as defined in  claim 1  which comprises: 
       (a) reacting a corresponding compound of formula (II)                    
        wherein R 1  is as defined in  claim 1  and R 3  is as defined in  claim 1  and L represents a leaving group, or a protected derivative thereof, with a compound of formula R 2 NH 2  or a protected derivative thereof, wherein R 2  is as defined in  claim 1 ;  
       (b) reacting a corresponding compound of formula (III)                    
        wherein R 1  is as defined in  claim 1  and R 2  is as defined in  claim 1 , with a compound of formula (IV)                    
        wherein R 3  is as defined in  claim 1  and L represents a leaving group or a protected derivative thereof;  
       (c) converting one compound of formula (I) to another compound of formula (I); or  
       (d) deprotecting a compound of formula (I) which is protected;  
       and where desired or necessary converting a compound of formula (I) or a salt thereof into another salt thereof. 
     
     
       24. A process for preparation of a compound of formula (I) as defined in  claim 1  which comprises reacting a corresponding compound of formula (IIa):                    
       wherein R 2  is as defined in  claim 1  and R 3  is as defined in  claim 1  and L represents a leaving group or a protected derivative thereof, with a compound of formula R 1 NH 2  or a protected derivative thereof, wherein R 1  is as defined in  claim 1 . 
     
     
       25. A compound of formula (II)                    
       wherein R 1  is as defined in  claim 1  and R 3  is as defined in  claim 1  and L represents a leaving group, or a protected derivative thereof. 
     
     
       26. A compound of formula (IIa)                    
       wherein R 2  is as defined in  claim 1  and R 3  is as defined in  claim 1  and L represents a leaving group, or a protected derivative thereof. 
     
     
       27. A compound of formula (IV)                    
       wherein R 3  is as defined in  claim 1  and L represents a leaving group or a protected derivative thereof. 
     
     
       28. A compound of formula (V)                    
       wherein R 3  is as defined in  claim 1 . 
     
     
       29. A compound of formula (V)                    
       wherein R 3  is as defined in  claim 1  and L 1  and L 2  independently represent a leaving group, or a protected derivative thereof. 
     
     
       30. A compound of formula (VIII) 1                     
       wherein R 1  is as defined in  claim 1  and L is a leaving group or a protected derivative thereof. 
     
     
       31. A compound of formula (IX) 1                     
       wherein R 1  is as defined in  claim 1  and R 3  is as defined in  claim 1  and L is a leaving group or a protected derivative thereof. 
     
     
       32. A compound of formula (X) 1                     
       wherein R 1  is as defined in  claim 1  and R 3  is as defined in  claim 1  and L is a leaving group or a protected derivative thereof. 
     
     
       33. A pharmaceutical composition comprising a compound of formula (I) as defined in  claim 16  or a pharmaceutically acceptable salt or solvate thereof in admixture with one or more physiologically acceptable diluents or carriers. 
     
     
       34. A pharmaceutical composition comprising a compound of formula (I) as defined in  claim 18  or a pharmaceutically acceptable salt or solvate thereof in admixture with one or more physiologically acceptable diluents or carriers. 
     
     
       35. A method of treatment or of inflammatory diseases which comprises administering to a patient an effective amount of a compound of formula (I) as defined in  claim 16  or a pharmaceutically acceptable salt or solvate thereof. 
     
     
       36. A method of treatment of inflammatory diseases which comprises administering to a patient an effective amount of a compound of formula (I) as defined in  claim 18  or a pharmaceutically acceptable salt or solvate thereof.